PROJECT SUMMARY/ABSTRACT This proposal outlines an early stage investigator grant (NIBIB Trailblazer R21) for the PI to develop optical technologies for real-time imaging of cerebral response to cardiac arrest (CA). CA affects over 550,000 people in the U.S., and 80-90% of survivors suffer severe neurological deficits due to altered cerebral hemodynamics.. There is a severe unmet clinical need for quantitative tools to monitor cerebral perfusion, metabolism, and neurovascular coupling during CA, cardiopulmonary resuscitation (CPR), and post-CPR. To meet this need, we will develop an optical imaging platform and validate it in a rat model of CA and CPR to generate new clinically-translational discoveries. This technology will be combined with quantitative electroencephalography (qEEG) and biomarkers in our unique pre-clinical intensive care setting. Our long term goal is to understand spatiotemporal changes in brain hemodynamics related to neurological outcome, to develop interventions to help CA patients. Our optical platform will provide real-time, co-registered multispectral spatial frequency domain imaging (SFDI) and laser speckle imaging (LSI) of critical neurovascular parameters: oxy- and deoxyhemoglobin, CBF, tissue scattering, and relative cerebral metabolic rate of oxygen consumption (rCMRO2). We will combine this with qEEG to monitor neurovascular coupling and subsequent neurological outcome parameters. The specific aims of this proposal focus on developing and validating this optical platform to investigate hyperdynamic cerebral perturbations, predict neurological recovery, and allow for intervention in real-time. Aim 1: Develop and validate a multimodal video-rate optical imaging platform for continuous monitoring of cerebral neurovascular response to CA and CPR. We will build video-rate LSI and SFDI instrumentation to measure pulsatile blood flow, absorption, and scattering in tissue. We will develop algorithms to co-register LSI and SFI during motion-prone periods, including CPR. We will validate the platform on tissue-simulating phantoms and an in vivo rat model to characterize dose responses to changes in cerebral hemodynamics and qEEG. Aim 2: Identify and modulate optical imaging parameters from CA to <40 min post-CPR that are predictive of neurologic recovery and test therapeutic potential of our imaging platform. We will modulate CBF and rCMRO2 to improve neural activity, and conversely, we will use neuro-stimulation to induce changes in CBF and rCMRO2 during CA and after CPR. This proposal will develop a video-rate optical platform that is uniquely capable of investigating neurovascular coupling during hyperdynamic periods of CA and CPR, with potential to improve post- CA survival. We plan to utilize these funds to develop a competitive R01 application for translation of our platform to the neurointensive care unit to ultimately improve neurological outcome after CA.